Krishna Vibhor, Fishman Paul S, Eisenberg Howard M, Kaplitt Michael, Baltuch Gordon, Chang Jin Woo, Chang Wei-Chieh, Martinez Fernandez Raul, Del Alamo Marta, Halpern Casey H, Ghanouni Pejman, Eleopra Roberto, Cosgrove Rees, Guridi Jorge, Gwinn Ryder, Khemani Pravin, Lozano Andres M, McDannold Nathan, Fasano Alfonso, Constantinescu Marius, Schlesinger Ilana, Dalvi Arif, Elias W Jeff
From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).
N Engl J Med. 2023 Feb 23;388(8):683-693. doi: 10.1056/NEJMoa2202721.
Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies.
We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months.
Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.
Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).
在开放标签研究中，单侧聚焦超声消融苍白球内侧节可减轻帕金森病的运动症状。
我们以3:1的比例将处于药物未起效状态且患有帕金森病伴异动症或运动波动及运动功能障碍的患者随机分组，分别接受针对身体症状最明显一侧的聚焦超声消融或假手术。主要结局是3个月时的反应，定义为在药物未起效状态下治疗侧的运动障碍协会统一帕金森病评定量表第三部分（MDS-UPDRS III）评分或药物起效状态下统一异动症评定量表（UDysRS）评分较基线至少降低3分。次要结局包括MDS-UPDRS各部分评分从基线到第3个月的变化。在3个月的盲法阶段后，开放标签阶段持续至12个月。
94例患者中，69例被分配接受超声消融（积极治疗），25例接受假手术（对照）；分别有65例患者和22例患者完成了主要结局评估。在积极治疗组中，45例患者（69%）有反应，而对照组为7例（32%）（差异为37个百分点；95%置信区间为15至60；P = 0.003）。在积极治疗组中有反应的患者中，19例仅符合MDS-UPDRS III标准，8例仅符合UDysRS标准，18例符合两个标准。次要结局的结果与主要结局基本一致。在积极治疗组中3个月时有反应且在12个月时接受评估的39例患者中，30例继续有反应。积极治疗组中与苍白球切开术相关的不良事件包括构音障碍、步态障碍、味觉丧失、视觉障碍和面部无力。
在3个月的时间里，单侧苍白球超声消融导致运动功能改善或异动症减轻的患者比例高于假手术，但伴有不良事件。需要进行更长时间和更大规模的试验来确定该技术在帕金森病患者中的效果和安全性。（由Insightec资助；ClinicalTrials.gov编号，NCT03319485。）
